Mechanisms contributing to the development of hypertension continue to be elucidated and recent evidence suggests a prominent role for the immune system and inflammation. Systemic lupus erythematosus (SLE) is a chronic inflammatory disorder estimated to affect nearly 2 million people in the United States, of which 90% are young women. While young healthy women have a low risk for developing hypertension, the prevalence of hypertension is very high in young women with SLE. Hypertension is a major cardiovascular risk factor, the predominant cause of mortality during SLE, and the mechanisms promoting elevated blood pressure during SLE are unknown. Previous work from my laboratory shows that renal inflammation contributes to hypertension in an established genetic mouse model of SLE. In addition, there is a rightward parallel shift in the chronic pressure natriuresis relationship and increased renal vascular resistance and renal vascular sensitivity to angiotensin II (AngII) suggesting that inflammation contributes to SLE hypertension though a renal vascular mechanism. The specific factors that contribute to the renal inflammation and hypertension are not clear. My preliminary data suggest that both systemic and renal T cell depletion reduces blood pressure in SLE mice and that CD4+ T cells (T helper) from SLE mice secrete more inflammatory cytokines [i.e., interleukin (IL)-17] than control T cells. Renal expression of the IL-17 receptor is also increased in SLE mice. Renal inflammation is associated with oxidative stress and I recently showed that oxidative stress mechanistically contributes to SLE hypertension. Based on this data, I will test the central hypothesis that T cells contribute to SLE hypertension through increased IL-17 production, which promotes oxidative stress leading to increased renal vascular sensitivity to AngII. The increased AngII sensitivity impairs renal hemodynamics (i.e., renal blood flow and renal vascular resistance) and leads to a decrease in the pressure natriuresis relationship that causes hypertension. Specific Aim 1 will test the hypothesis that T cells promote SLE hypertension through impairment of renal hemodynamics, leading to a shift in the pressure natriuresis relationship. Specific Aim 2 will test the hypothesis that T cell mediated production of IL-17 promotes renal oxidative stress and enhances renal vascular sensitivity to AngII. To investigate these aims, I will use state-of-the-art physiological, pharmacological, immunological, and biomolecular methods in mice. Taken together, data from the proposed studies will provide evidence of a mechanistic role of renal T lymphocytes in SLE hypertension.